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Bevacizumab Increases Viral Distribution in Human Anaplastic Thyroid Carcinoma Xenografts and Enhances the Effects of E1A-Defective Adenovirus dl922-947

Authors' Affiliations: ¹ Dipartimento di Biologia e Patologia Cellulare e Molecolare; ² Cattedra di Patologia Clinica Università Federico II; ³ Clinical Immunology and ⁴ Pathology, National Cancer Institute, Fondazione "G. Pascale," Naples, Italy; and ⁵ Cancer Research UK Molecular Oncology Unit, Barts and the London School of Medicine and Dentistry, London, United Kingdom

Requests for reprints: Giuseppe Portella, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia, Università di Napoli Federico II, Via S. Pansini 5, 80131 Naples, Italy. Phone: 39-81-746-3056; Fax: 39-81-746-3037; E-mail: portella{at}unina.it.

Purpose: Anaplastic thyroid carcinoma is a prime target for innovative therapy because it represents one of the most lethal human neoplasms and is refractory to conventional treatments such as chemotherapy and radiotherapy. We have evaluated a novel therapeutic approach based on the oncolytic replication-selective adenovirus dl922-947.

Experimental Design: The antitumor efficacies of the E1ACR2 (dl922-947) and E1B55K (dl1520) mutants were compared in human thyroid anaplastic carcinoma cells in culture and in xenografts in vivo. To enhance the effects of dl922-947, anaplastic thyroid carcinoma tumor xenografts were treated with dl922-947 in combination with bevacizumab.

Results: We showed that the efficacy of dl922-947 exceeded that of dl1520 in all tested anaplastic thyroid carcinoma cells in vitro and in vivo. Furthermore, bevacizumab in combination with dl922-947 significantly reduced tumor growth compared with single treatments alone. Bevacizumab treatment significantly improved viral distribution in neoplastic tissues.

Conclusions: Our data showed that dl922-947 had a higher oncolytic activity compared with dl1520 in anaplastic thyroid carcinoma cell lines and might represent a better option for virotherapy of anaplastic thyroid carcinoma. Moreover, bevacizumab increased the oncolytic effects of dl922-947 by enhancing viral distribution in tumors. The results described herein encourage the use of the dl922-947 virus in combination with bevacizumab.